Measuring and modelling agglomeration and breakage during agitated vacuum thermal drying
Over the last two decades considerable emphasis has been placed on the role API particle attributes play in both drug product performance and processability. The particle characterisation tool kit has expanded considerably and significant progress has been made in linking crystal structure with crystallization process design. However, the API isolation steps, filtration, washing and especially drying have not been subject to such intense investigation and have now become the “weak link in the chain”.
This PhD will deepen our understanding of the creation and subsequent breakage of granular APIs. The research objective is to understand and model the agglomeration processes which occur during drying and how these influence the evolution of; agglomerate size, size distribution and agglomerate strength during drying. The ultimate objective being to correlate measured attributes and process parameters with outcomes.
The PhD program will start with an evaluation of alternative approaches to describe the build-up of material at individual points of contact between crystals establishing necks of deposited material as the solvent evaporates. In parallel this two particle approach the student will develop a model for contact strength based on particle size, size distribution and crystal habit. Combining these two components the student will extend the model to multi-particle agglomerates / granules to investigate strength and breakage mode. Existing models from other fields of research will also be considered, in particular rheological insights from soil science will be reviewed and relevant approaches will be incorporated into the project.
Concerning the formation of granules, both static and agitated drying will be analysed, this will involve an experimental investigation, it is anticipated that this will focus on the effect of agitation and its absence at specific solvent contents in a series of highly constrained experiments. The role of temperature, solubility in the selected solvent, solvent properties, boiling point, vapour pressure, viscosity, interfacial tension and wettability with respect to the chosen API will be investigated. Drying kinetics will also be determined as a function of operating temperature, pressure and gas flow rate. In order to track the physical attributes of the API during drying a semi batch approach will be taken in which the same input material is dried to different end points then characterised. In this way the student will endeavour to model points of contact (eg using EDEM software), mass of material deposited over time, and explore stress analysis of agglomerates / granules leading to breakage.
In parallel a 10g scale bespoke agitated drier equipped with in-situ video and torque measurement will be operated to mimic operation in classical agitated filter driers. The overall object of the experimental program will be to develop an evaluation procedure to supply data into the model and to verify the output from the model.
An explicit model of the wetted neck between crystals and the capillary forces driving both neck formation and solute transport during drying will be built and used to predict the strength of the resulting solid bridge holding particles together.
In addition to undertaking cutting edge research, students are also registered for the Postgraduate Certificate in Researcher Development (PGCert), which is a supplementary qualification that develops a student’s skills, networks and career prospects.
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This PhD project is a fully funded iCASE award with AstraZeneca with EPSRC funding, applicants must meet the EPSRC funding criteria.
Students applying should have (or expect to achieve) a minimum 2.1 undergraduate degree in a relevant engineering/science discipline, and be highly motivated to undertake multidisciplinary research.